Long noncoding RNA HOXD-AS1 regulates proliferation of cervical cancer cells by activating Ras/ERK signaling pathway.

OBJECTIVE: To investigate the effects of HOXD cluster antisense RNA 1 (HOXD-AS1) in cervical cancer and its underlying mechanism. PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to examine the expression of HOXD-AS1 in human cervical cancer tissues. x2-test was used for analyzing the association of HOXD-AS1 expression and clinical parameters. Cell viability, colony formation capacity, and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) in treated HeLa and CaSki cells were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, colony formation assay, and Western blot analysis, respectively. RESULTS: The results indicated that HOXD-AS1 was upregulated in cervical cancer cells significantly. Meanwhile, HOXD-AS1 expression was involved in tumor-node-metastasis stages, lymphovascular invasion, lymph node metastasis, as well as recurrence. HOXD-AS1 knockdown remarkably suppressed cervical cancer cell proliferation, colony formation capacity, and the Ras/ERK signaling pathway in vitro. Furthermore, xenograft assays confirmed the results in vivo. CONCLUSIONS: Our data elucidate that silencing HOXD-AS1 remarkably suppresses cell growth by inactivating the Ras/ERK pathway in cervical cancer, providing a more detailed understanding of cervical cancer pathogenesis and providing a possible theoretical foundation for long non-coding RNA for the diagnosis and therapy for cervical cancer.

[Long-term outcome and prognostic factors in pregnant women with pulmonary arterial hypertension associated with congenital heart disease].

Objective: To investigate the perinatal outcome, risk factors and long-term outcome of pregnancy complicated with pulmonary arterial hypertension(PAH) and congenital heart diseases (CHD). Methods: Clinical data of 110 pregnant women who were diagnosed as PAH-CHD were retrospectively analyzed in the Department of Obstetrics and Gynecology and Surgical Intensive Care Unit at Beijing Anzhen Hospital from 2004 to 2013. The survival and treatment status were followed up. Results: 110 subjects consisted of 11 mild PAH, 33 moderate and 66 severe ones. The incidences of deterioration in New York Heart Association (NYHA) classes (≥2) during pregnancy, respiratory failure, pulmonary hypertension crisis and arrhythmia were 25.5% (28/110), 7.3% (8/110), 10.0% (11/110), 10.0% (11/110) respectively. Among them, the difference of deterioration in NYHA classes (≥2) during pregnancy among the three groups was statistically significant. A total of 8 (7.3%) maternal deaths occurred during hospitalization, all of whom were severe PAH cases. Multivariate analysis showed that pulmonary artery systolic pressure was a risk factor of perioperative death (OR=1.042, P=0.005). There were 55 cases (50.0%) of term delivery, and 35 cases (31.8%) of iatrogenic abortion. The proportion of term delivery in the severe PAH group was significantly lower. The proportion of iatrogenic abortion and small for gestational age infant (SGA) were higher in severe group. The incidence of neonatal malformations was 8.0% (6/75). The follow-up rate was 61.8% (63/102). Sudden death was reported in a parturient a few days after discharge. The remaining 62 patients survived during follow-up, while 53 patients (85.5%) were functional class (FC) Ⅰ-Ⅱ, 9 (14.5%) were FC Ⅲ-Ⅳ at follow-up. The cardiac function deterioration during pregnancy was not significantly correlated with long-term deterioration (P=0.767). Conclusions: Perinatal mortality and the incidence of maternal and fetal adverse events were high in pregnancy with PAH-CHD. Pulmonary artery systolic pressure is a major risk factor for perioperative mortality in pregnant women. PAH-CHD woman had good overall outcome after puerperium.

Host-species-dependent physiological characteristics of hemiparasite Santalum album in association with N2-fixing and non-N2-fixing hosts native to southern China.

Understanding the interactions between the hemiparasite Santalum album L. and its hosts has theoretical and practical significance in sandalwood plantations. In a pot study, we tested the effects of two non-N2-fixing (Bischofia polycarpa (Levl.) Airy Shaw and Dracontomelon duperreranum Pierre) and two N2-fixing hosts (Acacia confusa Merr. and Dalbergia odorifera T. Chen) on the growth characteristics and nitrogen (N) nutrition of S. album. Biomass production of shoot, root and haustoria, N and total amino acid were significantly greater in S. album grown with the two N2-fixing hosts. Foliage and root δ(15)N values of S. album were significantly lower when grown with N2-fixing than with non-N2-fixing hosts. Significantly higher photosynthetic rates and ABA (abscisic acid) concentrations were seen in S. album grown with D. odorifera. Similarity in the proportional amounts of amino acid of root xylem sap between S. album and its host D. odorifera was also evident, suggesting major access to nitrogenous solutes from D. odorifera to S. album. Irrespective of host species, S. album clearly appeared to optimize xylem sap extraction from its hosts by higher transpiration and lower water-use efficiency than its host. The growth of two non-N2-fixing hosts parasitized by S. album was significantly greater than the equivalent values for unparasitized treatments, and lower growth and photosynthesis were observed for parasitized A. confusa, and significant decreases in root N, photosynthesis and transpiration for parasitized D. odorifera compared with unparasitized treatments. Furthermore, foliage ABA concentrations were significantly higher in all hosts parasitized by S. album than in their unparasitized counterparts. Our study is probably the first to report on host dependence and preference in the hemiparasite S. album, and the generated results may have important implications for understanding of the physiological interactions between host species and parasitic plants, and for successfully mixing plantations of S. album with D. odorifera.

Timing of xenon-induced delayed postconditioning to protect against spinal cord ischaemia-reperfusion injury in rats.

BACKGROUND: This study was designed to assess the neuroprotective effect of xenon-induced delayed postconditioning on spinal cord ischaemia-reperfusion injury (IRI) and to determine the time of administration for best neuroprotection in a rat model of spinal cord IRI. METHODS: Fifty male rats were randomly divided equally into a sham group, control group, and three xenon postconditioning groups (n=10 per group). The control group underwent spinal cord IRI and immediately inhaled 50% nitrogen/50% oxygen for 3 h at the initiation of reperfusion. The three xenon postconditioning groups underwent the same surgical procedure and immediately inhaled 50% xenon/50% oxygen for 3 h at the initiation of reperfusion or 1 and 2 h after reperfusion. The sham operation group underwent the same surgical procedure without aortic occlusion, and inhaled 50% nitrogen/50% oxygen. Neurological function was assessed using the Basso, Beattie, and Bresnahan score at 4, 24, and 48 h of reperfusion. Histological examination was performed using Nissl staining and immunohistochemistry, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling staining. RESULTS: Compared with the control group, the three xenon postconditioning groups showed improvements in neurological outcomes, and had more morphologically normal neurones at 48 h of reperfusion. Apoptotic cell death was reduced and the ratio of Bcl-2/Bax immunoreactivity increased in xenon-treated rats compared with controls. CONCLUSIONS: Xenon postconditioning up to 2 h after reperfusion provided protection against spinal cord IRI in rats, but the greatest neuroprotection occurred with administration of xenon for 1 h at reperfusion.

Two-way transfer of nitrogen between Dalbergia odorifera and its hemiparasite Santalum album is enhanced when the host is effectively nodulated and fixing nitrogen.

Nutrient translocation from a host plant is vital to the growth and survival of its root parasitic plant, but few studies have investigated whether a parasitic plant is also able to transfer nutrients to its host. The role of N2-fixation in nitrogen (N) transfer between 7-month-old Dalbergia odorifera T. Chen nodulated with Bradyrhizobium elkanii DG and its hemiparasite Santalum album Linn. was examined by external (15)N labeling in a pot study. Four paired treatments were used, with (15)N given to either host or hemiparasite and the host either nodulated or grown on combined N. N2-fixation supplied 41-44% of total N in D. odorifera. Biomass, N and (15)N contents were significantly greater in both nodulated D. odorifera and S. album grown with paired nodulated D. odorifera. Significantly higher total plant (15)N recovery was in N donor D. odorifera (68-72%) than in N donor S. album (42-44%), regardless of the nodulation status in D. odorifera. Nitrogen transfer to S. album was significantly greater (27.8-67.8 mg plant(-1)) than to D. odorifera (2.0-8.9 mg plant(-1)) and 2.4-4.5 times greater in the nodulated pair than in the non-nodulated pair. Irrespective of the nodulation status, S. album was always the N-sink plant. The amount of two-way N transfer was increased by the presence of effective nodules, resulting in a greater net N transfer (22.6 mg plant(-1)) from host D. odorifera to hemiparasite S. album. Our results may provide N management strategies for D. odorifera/S. album mixed plantations in the field.

Post-conditioning by xenon reduces ischaemia-reperfusion injury of the spinal cord in rats.

BACKGROUND: The neuroprotective effects of xenon post-conditioning following spinal cord injury remain unknown. We monitored the effect of xenon post-conditioning on the spinal cord following ischaemia-reperfusion injury and determined its mechanism of action. METHODS: Spinal cord ischaemia was induced following balloon occlusion of the thoracic aorta in male Sprague-Dawley rats. Rats were divided into three groups (n = 30 in each group). The control group underwent ischaemia-reperfusion injury and immediately inhaled 50% (v/v) nitrogen at the time of reperfusion for 60 min continuously. The xenon-post-conditioning group underwent the same surgical procedure and immediately inhaled 50% (v/v) xenon at the time of reperfusion for 60 min continuously. The sham operation group underwent the same surgical procedure without aortic catheter occlusion and inhaled the same gas as that in control rats. Neurologic function was assessed using the Basso, Beattie, and Bresnahan score at 4, 24, and 48 h after reperfusion. Histological changes were observed using Nissl staining, the ultrastructure of the spinal cord was examined using transmission electron microscopy, and apoptosis was monitored using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling. RESULTS: Compared with the control group, the xenon-post-conditioning group showed improved neurologic outcomes (11.3 ± 1.6 vs. 15.7 ± 3.1, respectively) and had more morphologically normal neurons (6 ± 2 vs. 12 ± 3) at 48 h after reperfusion. Moreover, apoptotic cell death in xenon-treated rats was reduced when compared with control rats (18.29 ± 3.06 vs. 27.34 ± 3.63, P < 0.05, respectively). CONCLUSIONS: Xenon post-conditioning exerts a neuroprotective effect on the spinal cord following ischaemia-reperfusion injury via its anti-apoptotic role.

Effects of aging on luteinizing hormone secretion, ovulation, and ovarian tissue-type plasminogen activator expression.

This study examined the effects of aging on LH surge magnitude, ovulation, and ovarian expression of tissue-type plasminogen activator (tPA), a protease implicated in follicular rupture. While mean LH levels and ovulation rates were similar in middle-aged cyclic and young groups, there was a significant correlation between peak LH levels and ovulation rates in individual rats, such that females with lower LH surges ovulated fewer ova. In a separate experiment, proestrous LH levels were characterized in young and middle-aged rats, followed by in situ hybridization analysis of ovarian tPA mRNA. In young proestrous rats, tPA expression was observed in thecal-interstitial cells and oocytes, but not granulosa cells, prior to the LH surge. After the LH surge, there was a marked increase in tPA mRNA levels in granulosa cells of preovulatory, but not smaller follicles, peaking at 0200 hr estrus. By 0500 hr estrus, ovarian tPA expression declined, and ovulation had occurred. In contrast, LH-induced follicular tPA mRNA levels were dramatically lower in middle-aged rats with attenuated LH surges, and persisting preovulatory follicles were common in ovaries of these females on estrus morning. These findings suggest that age-related declines in ovulatory function result in part from altered induction of ovarian tPA expression, likely due to decreased proestrous LH secretion.

Molecular characterization of tetralogy of fallot within Digeorge critical region of the chromosome 22.

The purpose of this study was to determine whether the levels of heterozygosity and microdeletion of specific loci within the DiGeorge critical region (del22q11) are associated with different phenotypes of tetralogy of Fallot (TF). Examinations were conducted on 84 sporadic TF patients and their unaffected parents for del22q11, using the following 9 simple tandem repeat polymorphic microsatellite markers: D22S420, D22S427, D22S941, D22S944, D22S264, D22S311, D22S425, D22S303, D22S257. The microdeletions were confirmed using quantitative PCR with markers TUPLE1, exon 2 of the UFD1L gene, and D22S264; the boundaries of these microdeletions were estimated using genotypic analyses of the unaffected family members. The del22q11 was identified in 14 patients (16.6%). The boundary of the shortest region of deletion overlap (SRO) in these 14 TF patients was identified, proximally using D22S427 and distally using the TUPLE 1 gene. The deletion of exon 2 of the UFD1L gene and TUPLE1 gene was identified in 13 patients (13/14 cases; 93%). The SRO in TF patients with del22q11 was at or close to the ADU breakpoint and centromeric to the UFD1L gene. The level of heterozygosity for the marker D22S944 in TF patients without del22q11 (n = 70) was found to be significantly lower than expected. Overall, this study demonstrated the significantly low level of heterozygosity within DiGeorge critical region in TF patients with or without del22q11. Our results suggest that the genetic factors leading to DiGeorge/velocardiofacial syndrome might also be partly responsible for TF phenotypes.

The type I BMP receptor BmprIB is essential for female reproductive function.

Maintenance of female reproductive competence depends on the actions of several hormones and signaling factors. Recent reports suggest roles for bone morphogenetic proteins (BMPs) in early stages of folliculogenesis. A role for the type I BMP receptor BmprIB as a regulator of ovulation rates in sheep has been described recently, but little is known about the roles of BMP signaling pathways in other aspects of reproductive function. We report here that BMPRIB is essential for multiple aspects of female fertility. Mice deficient in BmprIB exhibit irregular estrous cycles and an impaired pseudopregnancy response. BmprIB mutants produce oocytes that can be fertilized in vitro, but defects in cumulus expansion prevent fertilization in vivo. This defect is associated with decreased levels of aromatase production in granulosa cells. Unexpectedly, levels of mRNA for cyclooxygenase 2, an enzyme required for cumulus expansion, are increased. BmprIB mutants also exhibit a failure in endometrial gland formation. The expression of BmprIB in uterine linings suggests that these defects are a direct consequence of loss of BMP signaling in this tissue. In summary, these studies demonstrate the importance of BMP signaling pathways for estrus cyclicity, estradiol biosynthesis, and cumulus cell expansion in vivo and reveal sites of action for BMP signaling pathways in reproductive tissues.

Influences of age and ovarian follicular reserve on estrous cycle patterns, ovulation, and hormone secretion in the Long-Evans rat.

This study examined the influences of aging and reduced ovarian follicular reserve on estrous cyclicity, estradiol (E(2)) production, and gonadotropin secretion. Young virgin and middle-aged (MA) retired breeder female rats were unilaterally ovariectomized (ULO) or sham operated (control). Unilateral ovariectomy of young rats reduced the ovarian follicular reserve by one-half, to a level similar to that found in MA controls. Unilateral ovariectomy of MA females reduced the follicular pool further, to one half of MA controls. The incidence of regular cyclicity was significantly lower in MA ULO females than in young controls, with intermediate cycle frequency in young ULO and MA controls. Among cyclic rats, the magnitude of the proestrous LH surge was highest in young controls, intermediate in young ULO rats and MA controls, and lowest in MA ULO females. Similarly, ovulation rates were highest in young controls, intermediate in young ULO rats and MA controls, and lowest in MA ULO females. While young ULO rats exhibited augmented secondary FSH surges on estrous morning, middle-aged ULO females displayed secondary FSH levels comparable to young controls. The effects of age and reduced follicle number on estrous cyclicity and gonadotropin secretion were not due to altered E(2) secretion, as preovulatory E(2) levels were similar among all groups. Thus, experimental reduction in the follicular reserve exerts acute effects on the preovulatory LH surge, ovulation rate, and estrous cyclicity in both young and MA rats. However, decreased follicle number increases FSH levels only in young rats, indicating aging-related alterations in the feedback regulation of FSH.

Production of transgenic live-bearing fish and crustaceans with replication-defective pantropic retroviral vectors.

Transgenic fish have been routinely produced by microinjecting or electroporating foreign DNA into one-cell stage embryos or unfertilized eggs. While both techniques are effective in producing transgenic fish species from which unfertilized or newly fertilized eggs can be easily obtained, these techniques are not applicable to live-bearing fish and many crustacean species where unfertilized or newly fertilized eggs are not readily available. In this paper, we describe a new method of introducing foreign DNA into the live-bearing fish, Poeciliposis lucida, and crayfish, Procambarus clarkii, by directly transforming the immature ovary or testis of these animals with replication-defective pantropic retroviral vectors carrying a reporter gene (neo(R)). A significant fraction of the progeny derived from these treated animals contains the neo(R) reporter gene, determined by a PCR-based assay. The PCR-positive individuals were crossed with nontransgenic individuals, and about 50% of the resulting progeny carried the transgene, suggesting that the F(1) animals are germline transgenic. Integration of the transgenes was confirmed by detecting the junction fragments of the genomic DNA associated with transgene constructs. The expression of reporter genes was detected by reverse transcription (RT) PCR assay. These results showed that foreign genes could be reproducibly transferred into live-bearing fish and crustaceans by directly transforming the immature gonads with replication-defective pantropic retroviral vectors.

Transgenic live-bearing fish and crustaceans produced by transforming immature gonads with replication-defective pantropic retroviral vectors.

Transgenic animals have been routinely produced by microinjecting or electroporating naked DNA into 1-cell-stage embryos or unfertilized eggs. However, these techniques are inapplicable to live-bearing fish and many crustacean species for which unfertilized or newly fertilized eggs are not readily obtainable. In the present study, replication-defective pantropic retroviral vectors carrying a reporter gene (neo(R) or beta-gal) were used to directly transform the immature ovary or testis of a live-bearing fish (Poeciliopsis lucida) and crayfish (Procambarus clarkii). The fraction of the progeny derived from these treated individuals shown to contain the neo(R) reporter gene by an assay based on polymerase chain reaction (PCR) was significant. The PCR-positive individuals were crossed with nontransgenic individuals, and about 50% of the resulting progeny carried the transgene, suggesting that the F(1) animals are germline transgenic. Integration of the transgenes was confirmed by detecting the junction fragments of the genomic DNA associated with transgene constructs. Expression of reporter genes was detected by a reverse transcription-nested PCR assay. These results showed that transgenic live-bearing fish and crustaceans could be easily produced by directly transforming the immature gonads with replication-defective pantropic retroviral vectors.

[Comparative clinical study on treatment of varicocele caused infertility by tongling granule and surgical operation].

OBJECTIVE: To observe the effect of Tongjing granule (TJG) in treating varicocele caused infertility. METHODS: Comparative observation was carried on 75 cases of male infertility caused by moderate or severe varicocele with abnormal semen, they were divided into two groups: the 44 patients in the TCM group treated with TJG and the 31 patients in the operation group treated by surgical operation (high ligation of spermatic vein and/or inferior epigastric venous bypass). All patients were followed up periodically to observe the amount, survival rate and activity of sperm by computerized automatic seminal analyser (CASA), as well as the occurrence of pregnancy in their partner. RESULTS: No significant difference was found in various parameters between the two groups. After treatment, the improvement of seminal density, amount of active sperms and forward moving sperms were lower in the TCM group than that in the operation group, but according to CASA, the improvement of TCM group is better than that of operation group. There was insignificance in the operation group between pre- and post-treatment, P > 0.05. CONCLUSION: TJG could treat the varicocele caused infertility with the clinical effect similar to the surgical operation, and was superior in improving motility of sperm. It indicates that surgical operation could only improve the local lesion, but TJG could modulate the general condition of patients also.

Effects of intrathecal morphine on the ventilatory response to hypoxia.

BACKGROUND: Intrathecal administration of morphine produces intense analgesia, but it depresses respiration, an effect that can be life-threatening. Whether intrathecal morphine affects the ventilatory response to hypoxia, however, is not known. METHODS: We randomly assigned 30 men to receive one of three study treatments in a double-blind fashion: intravenous morphine (0.14 mg per kilogram of body weight) with intrathecal placebo; intrathecal morphine (0.3 mg) with intravenous placebo; or intravenous and intrathecal placebo. The selected doses of intravenous and intrathecal morphine produce similar degrees of analgesia. The ventilatory response to hypercapnia, the subsequent response to acute hypoxia during hypercapnic breathing (targeted end-tidal partial pressures of expired oxygen and carbon dioxide, 45 mm Hg), and the plasma levels of morphine and morphine metabolites were measured at base line (before drug administration) and 1, 2, 4, 6, 8, 10, and 12 hours after drug administration. RESULTS: At base line, the mean (+/-SD) values for the ventilatory response to hypoxia (calculated as the difference between the minute ventilation during the second full minute of hypoxia and the fifth minute of hypercapnic ventilation) were similar in the three groups: 38.3+/-23.2 liters per minute in the placebo group, 33.5+/-16.4 liters per minute in the intravenous-morphine group, and 30.2+/-11.6 liters per minute in the intrathecal-morphine group (P=0.61). The overall ventilatory response to hypoxia (the area under the curve) was significantly lower after either intravenous morphine (20.2+/-10.8 liters per minute) or intrathecal morphine (14.5+/-6.4 liters per minute) than after placebo (36.8+/-19.2 liters per minute) (P=O.003). Twelve hours after treatment, the ventilatory response to hypoxia in the intrathecal-morphine group (19.9+/-8.9 liters per minute), but not in the intravenous-morphine group (30+/-15.8 liters per minute), remained significantly depressed as compared with the response in the placebo group (40.9+/-19.0 liters per minute) (P= 0.02 for intrathecal morphine vs. placebo). Plasma concentrations of morphine and morphine metabolites either were not detectable after intrathecal morphine or were much lower after intrathecal morphine than after intravenous morphine. CONCLUSIONS: Depression of the ventilatory response to hypoxia after the administration of intrathecal morphine is similar in magnitude to, but longer-lasting than, that after the administration of an equianalgesic dose of intravenous morphine.

Determination of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in plasma after intravenous and intrathecal morphine administration using HPLC with electrospray ionization and tandem mass spectrometry.

High-performance liquid chromatography (HPLC) coupled to atmospheric pressure ionization (API) mass spectrometry (MS) has become a useful technique in the direct analysis of low concentrations of conjugated opiate metabolites. Previous methods using HPLC with traditional detection methods do not have the sensitivity to detect low concentrations of most conjugated drug metabolites. Methods using gas chromatography-mass spectrometry (GC-MS) require hydrolysis and derivatization of the sample followed by an indirect quantitation of conjugated metabolites. Recently, several reports have described direct analysis of opiates and their glucuronide conjugates by HPLC and API-MS. These methods report lower limits of detection than GC-MS methods and quantitation in the low nanogram-per-milliliter range for the glucuronide metabolites of morphine. This report describes an HPLC-electrospray-MS-MS method capable of detecting subnanogram concentrations of morphine (MOR) and its 3- and 6-glucuronide metabolites (M3G and M6G, respectively). The assay has a dynamic range of 250-10,000 pg/mL for M3G and M6G and 500-10,000 pg/mL for MOR. Inter- and intra-assay precision and accuracy varied by less than 8% for all analytes at 750-, 2500-, and 7500-pg/mL concentrations. This assay was used for the determination of MOR, M3G, and M6G in human plasma after intravenous (i.v.) and intrathecal (i.t.) administration of MOR and its effects on the ventilatory response to hypoxia. Peak plasma concentrations of MOR and M6G were measured 1 h after i.v. administration of MOR. Peak concentrations of M3G were measured 2 h after i.v. administration of MOR. After i.t. administration of MOR, peak concentrations of M3G were measured 8 h postdose. MOR was not detected in plasma of patients administered MOR i.t.. Subnanogram concentrations of M6G were measured in the plasma of five of nine patients administered MOR i.t..

Delays in the detection of hypoxemia due to site of pulse oximetry probe placement.

STUDY OBJECTIVES: To determine if there were any differences in the time to detect hypoxemia related to the site of peripheral pulse oximetry (ear, hand, and foot) during the rapid induction of hypoxemia in healthy volunteers. DESIGN: Repeated-measures, longitudinal, observational study. SETTING: Anesthesia clinical research area of the Department of Anesthesiology. PATIENTS: 13 healthy volunteers, aged 18 to 44 years. INTERVENTIONS: Nellcor N-200 (Nellcor, Inc., Pleasanton, CA) oximeter probes were placed at the ear, hand, and foot. All units were turned on simultaneously with averaging times set for 5 seconds and signals sampled at 2 Hz. A computer-controlled anesthesia circuit was employed to induce mild hypercapnia and hyperoxia (end-tidal gas partial pressures: PETCO2 = 42 +/- 2 mmHg and PETO2 = 130 mmHg) for 5 minutes. PETO2 was then decreased to 45 +/- 2 mmHg over 60 seconds and held at that value for 5 minutes. MEASUREMENTS AND MAIN RESULTS: The mean differences in time (sec) for pulse oximeters to detect hypoxemia (read less than 90%) between probe sites were determined and compared. The following mean differences in time (sec) for pulse oximeters to detect hypoxemia (read less than 90%) between probe sites were found: ear-hand = 6; hand-foot = 57; ear-foot = 63. Paired t-tests revealed statistically significant mean time delay differences of 51 seconds (p < 0.005) and 57 seconds (p < 0.005) for ear-hand versus hand-foot and for ear-hand versus ear-foot, respectively. CONCLUSIONS: In healthy volunteers, significant delays in the detection of acute hypoxemia by pulse oximetry occur when pulse oximeters are placed at the toe as compared with probes at either the ear or hand.

Progesterone implants delay age-related declines in regular estrous cyclicity and the ovarian follicular reserve in Long-Evans rats.

The present study examined the effects of progesterone (P4) treatments on estrous cyclicity and the loss of ovarian follicles during aging. Young rats received repeated treatments with P4 or empty implants between 3.5 and 8 mo of age. At 8 mo, ovaries were obtained from some animals to determine the numbers of resting follicles, and estrous cycle patterns and hormone levels were determined from other groups of treated females. In contrast to the cyclic increases in P4, estradiol (E2), LH, and FSH in control animals, P4-implanted rats exhibited elevated serum P4 but low E2, LH, and FSH levels. After implant treatments, the follicular reserve was significantly (p < 0.05) larger in P4-treated females (2012 +/- 297 resting follicles per ovary, n = 5 rats per group) than in regularly cyclic control rats (713 +/- 226 follicles per ovary, n = 7). The effects of P4 implants on the follicular reserve were associated with a subsequently higher incidence of regular estrous cycles after P4 treatment. These results demonstrate that P4 prevents cyclic increases in E2 secretion and is associated with a conservation of the ovarian follicular reserve and the maintenance of regular estrous cycle patterns, indicating a protective effect of P4 on the age-related loss of ovarian follicles.

Influences of age and reproductive status on ovarian ovulatory responsiveness to gonadotropin stimulation.

Reproductive aging in the female rat is associated with the gradual loss of regular ovulatory function, decreased fertility, and smaller litter sizes. In the present study, we assessed ovarian ovulatory responsiveness to exogenous gonadotropin stimulation in young and middle-aged cyclic females and in middle-aged acyclic persistent-estrous (PE) rats. The ovulatory response to human chorionic gonadotropin (hCG) was dose-dependent in both young and middle-aged cyclic rats, with the percentages of rats ovulating and the numbers of ova shed per rat increasing with the dose of hCG administered. At the highest dose tested (10 mIU hCG/g bw), the range in ovulation rates among middle-aged cyclic rats (0-18 ova shed/rat) was greater than that in young animals (12-18 ova/rat). However, there were no statistically significant differences in either the percentages of females ovulating or in the mean ovulation rates between young and middle-aged cyclic groups. In contrast to the normal ovulatory responses observed in most middle-aged cyclic animals, response to hCG was markedly impaired in PE females of the same age. Middle-aged PE rats consistently failed to ovulate in response to a dose of hCG (10 mIU/g bw), which elicited high ovulation rates in young rats. At an even higher dose (20 mIU/g bw), only minimal ovulatory responses were observed (1.8 +/- 0.8 ova/rat; 80% of rats ovulating). Thus, most middle-aged regularly cyclic females maintain a similar ovulatory responsiveness to hCG as young rats, suggesting that decreased ovulation rates during aging may be related to attenuated preovulatory LH surges. However, impaired ovulatory responses were observed in middle-aged PE females, indicating altered ovarian function in acyclic animals, which may contribute to their anovulatory state.